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Background: Identification of risk factors and causes of stroke is key to optimize treatment and prevent recurrence. Up to one-third of young patients with stroke have a cryptogenic stroke according to current classification systems (Trial of ORG 10172 in Acute Stroke Treatment [TOAST] and atherosclerosis, small vessel disease, cardiac pathology, other causes, dissection [ASCOD]). The aim was to identify risk factors and leads for (new) causes of cryptogenic ischemic stroke in young adults, using the pediatric classification system from the IPSS study (International Pediatric Stroke Study). Methods: This is a multicenter prospective cohort study conducted in 17 hospitals in the Netherlands, consisting of 1322 patients aged 18 to 49 years with first-ever, imaging confirmed, ischemic stroke between 2013 and 2021. The main outcome was distribution of risk factors according to IPSS classification in patients with cryptogenic and noncryptogenic stroke according to the TOAST and ASCOD classification. Results: The median age was 44.2 years, and 697 (52.7%) were men. Of these 1322 patients, 333 (25.2%) had a cryptogenic stroke according to the TOAST classification. Additional classification using the ASCOD criteria reduced the number patients with cryptogenic stroke from 333 to 260 (19.7%). When risk factors according to the IPSS were taken into account, the number of patients with no potential cause or risk factor for stroke reduced to 10 (0.8%). Conclusions: Among young adults aged 18 to 49 years with a cryptogenic ischemic stroke according to the TOAST classification, risk factors for stroke are highly prevalent. Using a pediatric classification system provides new leads for the possible causes in cryptogenic stroke, and could potentially lead to more tailored treatment for young individuals with stroke.

Background Cerebral small vessel disease (SVD) is cross-sectionally associated with gait disturbances, however, the relation between baseline SVD and gait decline over time is uncertain. Furthermore, diffusion tensor imaging (DTI) studies on gait decline are currently lacking. Objective To investigate the association between baseline imaging SVD markers and gait decline. Methods In 2006, 310 participants from the RUN DMC cohort, a prospective cohort with older adults aged 50–85 years with SVD, were included. Gait variables were assessed using a computerized walkway during baseline and follow-up. Linear and logistic regression analyses were used to investigate the relation between imaging measures and gait decline and incident gait impairment (speed ≤ 1.0 m/s). Tract-based spatial statistics (TBSS) was used to identify possible differences in DTI measures of white matter tracts between participants with and without incident gait impairment. Results Mean age was 63.3 years (SD: 8.4) and mean follow-up duration 5.4 years (SD: 0.2). No significant associations between imaging measures and gait decline were found. TBSS analysis revealed no significant differences in DTI measures between participants with and without incident gait impairment after additional adjustment for SVD. In sub-analyses, a high total WMH volume (OR: 2.8 for highest quartile, 95% CI: 1.1–7.1) and high infratentorial WMH volume (OR: 1.8 per SD increase, 95% CI: 1.1–2.9) were associated with an increased 5-year risk of gait impairment, although this was not significant after correction for multiple testing. Conclusion Baseline imaging SVD markers were not associated with gait decline or incident gait impairment after 5 years. Future studies should investigate if SVD progression is related to gait deterioration.

Background and Purpose— In patients harboring intracranial aneurysms, the major goal in treatment is to prevent bleeding. A new generation of an endoluminal device (Surpass Flow Diverter [Surpass]) was developed to reconstruct parent artery and occlude the aneurysm. We present our clinical and angiographic single-center experience. Methods— Patients with a wide range of complex unruptured aneurysms were treated with the Surpass placed in the parent artery and bridging the aneurysm. Clinical and angiographic follow-up were performed at 6 months. Data were prospectively collected. Results— Thirty seven patients (mean age, 56 years; range, 32–79), harboring 49 unruptured aneurysms were treated at our center. All except 1 patient were treated with a single device. Successful delivery of the device was achieved in all patients. All 35 nonbifurcation aneurysm necks were covered completely, whereas 14 bifurcation aneurysms were only partially covered. There was no major periprocedural morbidity or mortality. During follow-up, 4 patients (10.4%) experienced transient neurological deficit. One patient (3%) developed a minor stroke at 4-month follow-up with persistent neurological deficit. Twelve patients had neurological symptoms related to their aneurysm and 7 showed improvement of these symptoms during follow-up. At 6-month follow-up, 29 of 31 aneurysms studied that had complete neck coverage showed a complete occlusion (94%) including 1 case with a 95% to 100% occlusion, whereas 5 of the 10 bifurcation aneurysms were occluded. Conclusions— Our study shows high safety and efficacy profile of a new generation endoluminal device in treatment of complex intracranial aneurysms. Long-term studies of treated bifurcation aneurysms are needed.

Contains fulltext : 116858.pdf (Publisher’s version ) (Closed access) Cerebral small vessel disease (SVD), including white matter lesions (WML) and lacunar infarcts, is related to objective cognitive impairment but also to subjective cognitive failures (SCF). SCF have reported to be an early predictor of dementia. Cerebral microbleeds (MB) are another manifestation of SVD and have been related to cognitive impairment, but the role of MB in SCF has never been studied. We therefore investigated whether MB are related to SCF among non-demented elderly individuals with SVD, independent of coexisting WML and lacunar infarcts. The RUN DMC study is a prospective cohort study among 503 older persons with cerebral SVD between 50 and 85 years of age. All participants underwent FLAIR and T2* scanning. SCF, subjective memory failures (SMF), and subjective executive failures (SEF) were assessed. The relation between SCF and the presence, number and location of MB was assessed by linear regression analyses adjusted for age, sex, education, depressive symptoms, cognitive function, total brain volume, normalized hippocampal volume, territorial infarcts, WML, and lacunar infarcts. MB were present in 11%. We found a relation between the presence, total number and lobar located MB, and SCF, SMF, and SEF and the reported progression of these failures, especially in participants with good objective cognitive function. In conclusion, MB are related to SCF independent of co-existing WML and lacunar infarcts, especially in those with good objective cognitive performance. These results suggest that MB are associated with the earliest manifestations of cognitive impairment. MB may help us to understand the role of the ever-expanding spectrum of SVD in cognitive impairment. 6 p.

Background Cerebral small vessel disease (SVD) is very common in elderly and related to cognition, although this relation is weak. This might be because the underlying pathology of white matter lesions (WML) is diverse and cannot be properly appreciated with conventional FLAIR MRI. In addition, conventional MRI is not sensitive to early loss of microstructural integrity of the normal appearing white matter (NAWM), which might be an important factor. Diffusion tensor imaging (DTI) provides alternative information on microstructural white matter integrity and we have used this to investigate the relation between white matter integrity, in both WML and NAWM, and cognition among elderly with cerebral SVD. Methods The RUN DMC study is a prospective cohort study among 503 independently living, non-demented elderly with cerebral SVD aged between 50 and 85 years. All subjects underwent MRI and DTI scanning. WML were segmented manually. We measured mean diffusivity (MD) and fractional anisotropy (FA), as assessed by DTI in both WML and NAWM. Results Inverse relations were found between MD in the WML and NAWM and global cognitive function (β = −.11, p Conclusion DTI parameters in both WML and NAWM correlate with cognitive performance, independent of SVD. DTI may be a promising tool in exploring the mechanisms of cognitive decline and could function as a surrogate marker for disease progression in therapeutic trials. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Background and Purpose— Mild parkinsonian signs (MPS) are common in elderly people and may be an early stage of parkinson(ism). They might be related to cerebral small-vessel disease, although this association remains incompletely understood. To identify subjects at early stages of the disease, we investigated whether the presence of MPS was dependent on the severity and location of small-vessel disease, including white matter lesions and lacunar infarcts. Methods— Four hundred thirty individuals, with small-vessel disease, aged between 50 and 85 years, without dementia or parkinsonism, were included in this analysis and underwent MRI scanning. The number and location of lacunar infarcts were rated. White matter lesion volume was assessed by manual segmentation with automated delineating of different regions. Presence of MPS was based on the motor section of the Unified Parkinson's Disease Rating Scale. Associations were determined using logistic regression analysis adjusted for age, sex, and total brain volume. Results— Severe white matter lesions and the presence of lacunar infarcts were independently associated with the presence of MPS (OR, 2.6; 95% CI, 1.3–4.9 and OR, 1.8; 95% CI, 1.0–3.0). Frontal and parietal white matter lesions and, to a lesser extent, lacunar infarcts in the thalamus were associated with a higher risk of MPS. The presence of lacunar infarcts was independently related to the bradykinesia category of parkinsonian signs. Conclusions— This study shows that severe small-vessel disease, especially at certain locations, is associated with MPS signs in older adults. Our findings suggest that small-vessel disease interrupts basal ganglia–thalamocortical circuits involving both the frontal and parietal lobes and hence may result in MPS.

Contains fulltext : 110720.pdf (Publisher’s version ) (Closed access) Although gait disturbances are present in a substantial portion of patients with cerebral small vessel disease (SVD), their pathogenesis has not been clarified as they are not entirely explained by the white matter lesions (WMLs) and lacunar infarcts. The role of cortical thickness in these patients remains largely unknown. We aimed to assess the regions of cortical thickness associated with distinct gait parameters in patients with SVD, and whether these associations were dependent on WMLs and lacunar infarcts. MRI data were obtained from 415 subjects with SVD, aged between 50 and 85 years. We assessed cortical thickness using surface-based cortical thickness analysis, and gait performance using the GAITRite system. Cortical thickness of predominantly the orbitofrontal and ventrolateral prefrontal cortex, the inferior parietal lobe, cingulate areas and visual association cortices was positively related to stride length. Thickness of the primary and supplementary motor cortices and the cingulate cortex was positively related to cadence, while thickness of the orbitofrontal and ventrolateral prefrontal cortex, anterior cingulate cortex and especially the inferior parietal lobe and superior temporal gyrus was negatively related to stride width. The associations with stride length and width were partially explained by the subcortical WMLs and lacunar infarcts. Cortical thickness may therefore be important in gait disturbances in individuals with SVD, with different cortical patterns for specific gait parameters. We suggest that cortical atrophy is part of the disease processes in patients with SVD. 7 p.

Contains fulltext : 95719.pdf (Publisher’s version ) (Closed access) Cigarette smoking doubles the risk of dementia and Alzheimer's disease. Various pathophysiological pathways have been proposed to cause such a cognitive decline, but the exact mechanisms remain unclear. Smoking may affect the microstructural integrity of cerebral white matter. Diffusion tensor imaging is known to be sensitive for microstructural changes in cerebral white matter. We therefore cross-sectionally studied the relation between smoking behaviour (never, former, current) and diffusion tensor imaging parameters in both normal-appearing white matter and white matter lesions as well as the relation between smoking behaviour and cognitive performance. A structured questionnaire was used to ascertain the amount and duration of smoking in 503 subjects with small-vessel disease, aged between 50 and 85 years. Cognitive function was assessed with a neuropsychological test battery. All subjects underwent 1.5 Tesla magnetic resonance imaging. Using diffusion tensor imaging, fractional anisotropy and mean diffusivity were calculated in both normal-appearing white matter and white matter lesions. A history of smoking was associated with significant higher values of mean diffusivity in normal-appearing white matter and white matter lesions (P-trend for smoking status = 0.02) and with poorer cognitive functioning compared with those who never smoked. Associations with smoking and loss of structural integrity appeared to be strongest in normal-appearing white matter. Furthermore, the duration of smoking cessation was positively related to lower values of mean diffusivity and higher values of fractional anisotropy in normal-appearing white matter [beta = -0.004 (95% confidence interval -0.007 to 0.000; P = 0.03) and beta = 0.019 (95% confidence interval 0.001-0.038; P = 0.04)]. Fractional anisotropy and mean diffusivity values in normal-appearing white matter of subjects who had quit smoking for >20 years were comparable with subjects who had never smoked. These data suggest that smoking affects the microstructural integrity of cerebral white matter and support previous data that smoking is associated with impaired cognition. Importantly, they suggest that quitting smoking may reverse the impaired structural integrity.

Background and Purpose— Hypertension is a risk factor for cerebral small vessel disease, which includes white matter lesions (WML) and lacunar infarcts. These lesions are frequently observed on MRI scans of elderly people and play a role in cognitive decline. Preferably, one would like to evaluate the effect of hypertension before fluid-attenuated inversion recovery visible macrostructural lesions occur, possibly by investigating its effect on the microstructural integrity of the white matter. Diffusion tensor imaging provides measures of structural integrity. Methods— In 503 patients with small vessel disease, aged between 50 and 85 years, we cross-sectionally studied the relation between blood pressure, hypertension, and hypertension treatment status and diffusion tensor imaging parameters in both normal-appearing white matter (NAWM) and WMLs. All of the subjects underwent 1.5-T MRI and diffusion tensor imaging scanning. Fractional anisotropy and mean diffusivity were calculated in both NAWM and WMLs. Results— Increased blood pressure and hypertension were significantly related to lower fractional anisotropy in both NAWM and WMLs and to higher mean diffusivity in WMLs. For hypertensives, odds ratios for the risk of impaired microstructural integrity (fractional anisotropy) were 3.1 (95% CI: 1.8 to 5.7) and 2.1 (95% CI: 1.2 to 3.5) in NAWM and WMLs, respectively, compared with normotensives. Fractional anisotropy odds ratios for treated uncontrolled subjects were 6.5 (95% CI: 3.3 to 12.7) and 2.7 (95% CI: 1.5 to 5.1) in NAWM and WMLs, respectively, compared with normotensives. Conclusions— Our data show that diffusion tensor imaging may be an appropriate tool to monitor the effect of blood pressure and the response to treatment on white matter integrity, probably even before the development of WMLs on fluid-attenuated inversion recovery.

Background and Purpose— Gait disorders are common in the elderly and are related to loss of functional independence and death. White matter lesions (WMLs) may be related, but only a minority of individuals with WMLs has gait disorders. Probably other factors are involved, including location and the independent effect of frequently coinciding lacunar infarcts, the other aspect of cerebral small vessel disease. The aim of our study was to investigate the effect of both the severity and location of both WMLs and lacunar infarcts on gait. Methods— Four hundred thirty-one independently living, nondemented elderly aged between 50 and 85 years with cerebral small vessel disease were included in this analysis and underwent MRI scanning. The number and location of lacunar infarcts were rated and WML volume was assessed by manual segmentation with automated delineating of different regions. Gait was assessed quantitatively with an electronic walkway as well as the semiquantitatively Tinetti and Timed-Up-and-Go test. Results— WMLs and lacunar infarcts were both independently associated with most gait parameters with stride length as the most sensitive parameter related to WMLs. WMLs in the sublobar (basal ganglia/internal capsule) and limbic areas and lacunar infarcts in the frontal lobe and thalamus were related to a lower velocity. Conclusions— Cerebral small vessel disease is related to gait disturbances. Because small vessel disease may, in part, be preventable, it should be regarded as a potentially important target for postponing gait impairment.

Contains fulltext : 89824.pdf (Publisher’s version ) (Closed access) Emerging noninvasive neuroimaging techniques allow for the morphometric analysis of patterns of gray and white matter degeneration in vivo, which may help explain and predict the occurrence of cognitive impairment and Alzheimer's disease. A single center prospective follow-up study (Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort study (RUN DMC)) was performed involving 503 nondemented elderly individuals (50-85 years) with a history of symptomatic cerebral small vessel disease (SVD). Age was associated with a global reduction in cortical thickness, and this relationship was strongest for ventrolateral prefrontal cortex, auditory cortex, Wernicke's area, superior temporal lobe, and primary visual cortex. Right and left hemispheres differed in the thickness of language-related areas. White matter (WM) lesions were generally negatively correlated with cortical thickness, primarily in individuals over the age of 60, with the notable exception of Brodmann areas 4 and 5, which were positively correlated in age groups 50-60 and 60-70, respectively. The observed pattern of age-related decline may explain problems in memory and executive functions, which are already well documented in individuals with SVD. The additional gray matter loss affecting visual and auditory cortex, and specifically the head region of primary motor cortex, may indicate morphological correlates of impaired sensory and motor functions. The paradoxical positive relationship between WM lesion volume and cortical thickness in some areas may reflect early compensatory hypertrophy. This study raises a further interest in the mechanisms underlying cerebral gray and white matter degeneration in association with SVD, which will require further investigation with diffusion weighted and longitudinal MR studies. 01 december 2010